Objective To analyze the glucolipotoxicity effects of glucose combined with free fatty acid (FFA) on ketone production and ultrastructure of skeletal muscle, by exogenous elevating circulating glucose and FFA concentration. Methods Fifty Wistar rats were divided into high-fat-feed induced obesity group (OB group, n=40) and ordinary feed as normal control group (NC group, n=10). Circulating glucose and FFA levels were increased by infusion in high-fat-fed obese rats. The levels of serum lipid, plasma FFA and beta-hydroxybutyric acid were detected by the horizontal colorimetry, and the microstructure of skeletal muscle was observed by transmission electron microscopy, especially the changes of the mitochondrial structure. Euglycemic-hyperinsulinemic clamp with tracer infusion was performed to assess peripheral insulin sensitivity. Results The average weight and body fat ratio in the OB group was higher than that in the NC group (P<0.05). Insulin clamp test to assess peripheral insulin sensitivity showed that the steady-state glucose Infusion rate in the OB group during clamp test was significantly lower than that in the NC group [OB: (19.26±1.84) mg/(kg·min)vs. NC: (28.82±1.69) mg/(kg·min), P<0.05]. The mitochondrial denaturation of skeletal muscle in the OB group of rats was observed, and the swelling and crest permutation, the accumulation of lipid droplets and cavitation were formed, and hypertrophy of mitochondria were also seen after intralipid and glucose infusion, which was obvious in the combined infusion group. Conclusions By exogenous elevating circulating glucose and FFA concentration, the products of ketone body increases. The mitochondrial damage of skeletal muscle suggests that mitochondrial may be the potential target of glucoxicity and lipotocicity.
To compare the platelet enrichment ratio of platelet-rich plasma (PRP) prepared by different centrifuge methods and to compare the concentration of growth factors released from autologous platelet-rich gel (APG) with the whole blood. Methods Thirteen diabetic patients with refractory skin lesions were enrolled in APG treatment. ① Three kinds of centrifuge methods were selected for PRP by 11 diabetic patients: A(n=6): 529 × g for 4 minutes in the first centrifugeand 854 × g for 6 minutes in the second centrifuge; B (n=5): 313 × g for 4 minutes in the first centrifuge and 1 252 × g for 6 minutes in the second centrifuge; C (n=5): 176 × g for 5 minutes in the first centrifuge and 1 252 × g for 5 minutes in the second centrifuge. Platelet counted on the whole blood and PRP was determined. The APG, produced by combining the PRPwith thrombin and calcium gluconate (10 ∶ 1) was used by patients. ② PDGF-BB, TGF-β1, VEGF, EGF, and IGF-1 were measured in the APG and the whole blood using the enzyme-l inked immunosorbent assay method. Results ① The average platelet concentration was higher in group B [(1 363.80 ± 919.74) × 109/ L] than in groups A[(779.67 ± 352.39) × 109/ L)] and C[(765.00 ± 278.78) × 109/ L] and the platelet recovery rate was 75.2% ± 21.0% in group B. ② The concentration of growth factors all increased with the increasing platelet number. On average, for the whole blood as compared with APG, the PDGF-BB concentration increased from (145.94 ± 133.24) pg/mL to (503.81 ± 197.86) pg/mL (P lt; 0.05); TGF-β1 concentration increased from (3.31 ± 2.27) ng/mL to (5.67 ± 4.80) ng/mL (P lt; 0.05); IGF-1concentration increased from (14.54 ± 35.34) ng/mL to (110.56 ± 84.36) ng/mL (P lt; 0.05); and EGF concentration increased from (160.73 ± 71.10) pg/mL to (265.95 ± 138.43) pg/mL (P lt; 0.05). No increase was found for VEGF(P gt; 0.05). ③ There was positive correlation between the platelet concentration and PDGF-BB and TGF-β1 (r = 0.627, r = 0.437, P lt; 0.05). ④ Thirteen diabetic repractory dermal ulcers received APG treatment for 18 times, 9 ulcers (69.2%) and 10 sinuses (88.3%) were cured at the end of 12-week treatment. Conclusion The method ofgroup B is the best centrifuge method. A variety of growth factors are detected and released from the platelets at significant levels in APG. There is positive correlation between the platelet concentration and PDGF-BB and TGF-β1 .
【摘要】 目的 探討胰島素強化治療對2型糖尿病（type 2 diabetes mellitus，T2DM）患者血清脂聯素（adiponectin，APN）的影響。 方法 2007年7—12月，研究納入連續使用胰島素治療至少3個月但血糖控制欠佳[6.5%≤糖化血紅蛋白（hemoglobin A1c， HbA1c）≤11.0%]的T2DM患者40例，其中男18例，女22例；年齡29~〖JP2〗69歲；平均診斷T2DM病史11年。治療方案為進行16周的胰島素強化治療，血糖控制目標為空腹血糖≤7 mmol/L，〖JP〗餐后2 h血糖≤8 mmol/L。分別于強化治療前、強化治療4周后及強化治療16周后測定HbA1c以及血清APN水平。 結果 與強化治療前相比，胰島素治療4周后空腹及三餐后2 h血糖明顯下降（Plt;0.05），但HbA1c和血清APN水平差異無統計學意義（Pgt;0.05）；強化16周后，HbA1c水平明顯低于治療前和治療4周后且差異具有統計學意義（Plt;0.05），APN水平高于治療前和治療4周后且差異有統計學意義（Plt;0.05）。體質量指數在強化治療16周后明顯增加且與強化治療前和強化治療后4周相比差異具有統計學意義（Plt;0.05）。APN與空腹血糖（b=-0.225，P=0.013）、早餐后2 h血糖（b=-0.229，P=0.012）呈負相關。 結論 胰島素強化治療可以提高T2DM患者血清APN水平。【Abstract】 Objective To investigate the effect of intensive insulin therapy on serum adiponectin (APN) level in patients with type 2 diabetes mellitus (T2DM). Methods Forty patients with T2DM who had undergone insulin therapy for at least three months but with their blood glucose poorly controlled [glycosylated hemoglobin Alc (HbA1c) level ranged from 6.5% to 10.0%] from July to December 2007 were enrolled in this study. There were 18 males and 22 females with their age ranged from 29 to 69 years. They had an average time of T2DM history of 11 years. Intensive insulin therapy was carried out for 16 weeks with a target of less than 7 mmol/L for fasting blood glucose and 8 mmol/L for postprandial blood glucose. HbA1c and serum adiponectin concentrations were detected at baseline, at week 4 after intensive therapy and at the end of the study. Results After 4 weeks of intensive blood glucose control, fasting and postprandial blood glucose levels decreased significantly (Plt;0.05), but the HbA1c and serum APN concentrations did not reduce remarkably (Pgt;0.05). After 16 weeks of treatment, the level of HbA1c was significantly lower than those at baseline and 4 weeks after treatment (Plt;0.05), and serum APN concentration increased significantly (Plt;0.05), compared with those two time points. However, an evident increase of body mass index (BMI) was found while compared with BMI at baseline and 4 weeks after treatment (Plt;0.05). The linear regression analysis indicated that APN was negatively associated with fasting blood glucose (b=-0.225,P=0.013) and blood glucose level 2 hours after breakfast (b=-0.229,P=0.012). Conclusion Intensive insulin therapy can improve serum adiponectin level in type-2 diabetic patients.
【摘要】 目的 調查成都地區2型糖尿病患者糖耐量正常一級親屬的代謝狀態及與胰島素抵抗、胰島β細胞功能的相關性。 方法 2007年7-9月共納入糖耐量正常的一級親屬312例（NGT-FDR組），無家族史的正常對照1 348例（NGT-C組）。測量兩組血壓、體重、腰圍；檢測口服葡萄糖耐量試驗（OGTT）中0、0.5、2 h血糖、胰島素水平；測定空腹血脂；計算體重指數、HOMA-胰島素抵抗指數（HOMA-IR）、胰島β細胞功能指數（HOMA-β），β細胞早相分泌功能指數（△I30/△G30），并比較兩組間上述指標的差異和代謝綜合征（MS）及其各組分的發病情況。 結果 ①NGT-FDR組MS發生率高于NGT-C組，發生MS的風險是后者的1.737倍。NGT-FDR組高甘油三酯血癥（hypertriglyceridemia，HTG）、空腹血糖偏高（5.6~6.0 mmol/L）的發生率高于NGT-C組，合并4種及以上代謝異常的幾率亦高于NGT-C組（Plt;0.05）；②年齡lt;40歲的NGT-FDR中心性肥胖、HTG、空腹血糖偏高和MS均高于同年齡對照；男性NGT-FDR空腹血糖偏高和MS發病率高于男性對照（Plt;0.05）；③腰圍、收縮壓（SBP）、空腹血糖（FBG）、甘油三酯（TG）及糖尿病家族史同HOMA-IR呈正相關。腰圍、SBP、TG及糖尿病家族史同HOMA-β呈正相關，FBG則同HOMA-β呈負相關。 結論 2型糖尿病糖耐量正常一級親屬比無家族史的對照表現出更多的代謝異常，尤其是在年齡lt;40歲及男性中。各種代謝異常可加重胰島素抵抗，影響胰島基礎分泌功能。故有必要對糖耐量正常的一級親屬進行各項代謝指標的監測和早期預防性干預。【Abstract】 Objective To investigate the metabolic status of the normal glucose-tolerant first-degree relatives (NGT-FDR) of type-2 diabetic patients and its relationship with insulin resistance (IR) and β-cell function in Chengdu area. Methods From July to September 2007, a total of 312 NGT-FDR of type-2 diabetic patients and 1 348 normal glucose tolerant controls without positive family history of diabetes (NGT-C) were enrolled in this study. Blood pressure, weight, waists, plasma glucose at hour 0, 1/2 and 2 in oral glucose tolerance test (OGTT), insulin levels and fasting blood lipids were measured. Body mass index (BMI), HOMA-IR, HOMA-β and the early insulin secreting index (△I30/△G30) were calculated. Then, we compared the above-mentioned data and the incidence of metabolic syndrome (MS) between the two groups. Results ①The incidence of MS, hypertriglyceridemia (HTG), higher fasting blood glucose (FBG) (5.6-6.0 mmol/L) in the NGT-FDR group were all significantly higher than those in the NGT-C group. The risk of developing MS in the NGT-FDR group was 1.737 times as high as that in the NGT-C group. Furthermore, the incidence of 4 or more than 4 co-existent metabolic disorders in the NGT-FDR group was also significantly higher than that in the NGT-C group (Plt;0.05); ②For subjects less than 40 years old, the incidence of central obesity, HTG, higher FBG and MS in the NGT-FDR group were all higher than those in the NGT-C group. In male subjects, the rates of higher FBG and MS were all significantly higher in the NGT-FDR group than those in the NGT-C group. (Plt;0.05); ③Waists, FBG, systolic blood pressure (SBP), triglycerides (TG) and diabetic family history were positively correlated with HOMA-IR. Waists, SBP, TG and diabetic family history were positively correlated with HOMA-β. Conclusion NGT-FDR present significantly increased metabolic disorders than NGT controls, especially in the less than 40-year-old and the male subjects. The metabolic disorders can aggravate insulin resistance and influence islet β-cell secretion function, so it is necessary to monitor the metabolic status of the NGT-FDR of type-2 diabetic patients and provide early preventive interventions.